Evidence map›Paper›PMID 40087637›Full record

ArticleBMC cancer2025

A genetically encoded fluorescent sensor enables sensitive and specific detection of IDH mutant associated oncometabolite D-2-hydroxyglutarate.

Kristian A Choate, Wren W L Konickson, Zoe L Moreno, Olivia S Brill, Brett C Cromell, Bella M Detienne, Matthew J Jennings, Paul B Mann, Robert J Winn, David O Kamson and 1 more

Abstract read
In one paragraph

Article in BMC cancer, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Kristian A ChoateDepartment of Biology, Northern Michigan University, Marquette, MI, USA.
Wren W L KonicksonDepartment of Chemistry, Northern Michigan University, Marquette, MI, USA.
Zoe L MorenoDepartment of Biology, Northern Michigan University, Marquette, MI, USA.
Olivia S BrillUpper Michigan Brain Tumor Center, Northern Michigan University, Marquette, MI, USA.
Brett C CromellUpper Michigan Brain Tumor Center, Northern Michigan University, Marquette, MI, USA.
Bella M DetienneDepartment of Biology, Northern Michigan University, Marquette, MI, USA.
Matthew J JenningsUpper Michigan Brain Tumor Center, Northern Michigan University, Marquette, MI, USA.
Paul B MannUpper Michigan Brain Tumor Center, Northern Michigan University, Marquette, MI, USA.
Robert J WinnDepartment of Biology, Northern Michigan University, Marquette, MI, USA.
David O KamsonDepartment of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Evan P S PrattUpper Michigan Brain Tumor Center, Northern Michigan University, Marquette, MI, USA. evpratt@nmu.edu.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

D-2-hydroxyglutarate (D-2-HG) is an oncometabolite that accumulates due to mutations in isocitrate dehydrogenase 1 and 2 (IDH1/2). D-2-HG may be used as a surrogate marker for IDH1/2 mutant cancers, yet simple and specific methods for D-2-HG detection are limited. Here, we present the development and characterization of a genetically encoded fluorescent sensor of D-2-HG (D2HGlo). D2HGlo responds to clinically relevant concentrations of D-2-HG, demonstrates exceptional selectivity and can quantify D-2-HG in various body fluids and glioma tumor supernatants. Additionally, analysis of tumor lysates using D2HGlo accurately predicted the IDH mutational status of gliomas. The successful quantification of D-2-HG within contrived samples suggests that D2HGlo may facilitate the detection and monitoring of IDH mutant cancers through liquid biopsies following further validation. In addition to D2HGlo's potential clinical utility, we also present findings for its adaptation to the cellular environment. To assess D-2-HG production in living immortalized glioma cells, we engineered D2HGlo sensors that localize to subcellular compartments, which yielded findings of elevated D-2-HG in the cytosol, mitochondria, and nucleus of IDH1 mutant cells. D2HGlo was used to perform a side-by-side comparison of cytosolic and secreted D-2-HG to reveal that glycolysis, but not glutamine catabolism, drives D-2-HG production in IDH1 mutant cells.

Indexed as

Biosensing TechniquesBrain NeoplasmsGliomaGlutaratesIsocitrate DehydrogenaseMutationCell Line, TumorFluorescent DyesHumansalpha-hydroxyglutarateFluorescent DyesGlutaratesIDH1 protein, humanIDH2 protein, humanIsocitrate DehydrogenaseD-2-hydroxyglutarateDiagnosticFluorescent biosensorGliomaIsocitrate dehydrogenase

Identifiers

PMID40087637
PMCPMC11909988

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.